Allyl bromide → Di-tert-butyl (2S,4S)-2-Allyl-4-(Boc-amino)pentanedioate

HRID 625828Notes

Reaction equation

HRID 625828 reaction equation
[C:1]([NH:8][C@H:9]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:10][CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH2:36](Br)[CH:37]=[CH2:38]>O1CCCC1>[CH2:38]([C@H:11]([C:12]([O:14][C:15]([CH3:16])([CH3:18])[CH3:17])=[O:13])[CH2:10][C@H:9]([NH:8][C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH:37]=[CH2:36]

Participants

5

Reactant 3

HCID 7841Allyl bromideHCID 2733832Lithium HexamethyldisilazideHCID 86647571Di-tert-butyl Boc-L-glutamate

Product 1

HCID 58185190Di-tert-butyl (2S,4S)-2-Allyl-4-(Boc-amino)pentanedioate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

26.96 g (75 mmol) of di-tert-butyl Boc-glutamate (Journal of Peptide Research (2001), 58, 338) were dissolved in 220 mL of tetrahydrofuran (THF) and cooled to −70° C. 165 mL (165 mmol) of a 1M solution of lithium bis(trimethylsilyl)amide in THF were added dropwise over a period of two hours at this temperature and the mixture was stirred at −70° C. for another 2 hours. 27.22 g (225 mmol) of allyl bromide were then added dropwise, and after 2 h at this temperature, the cooling bath was removed and 375 mL of 2N aqueous hydrochloric acid and 1.25 L of ethyl acetate were added. The organic phase was separated off, washed with water until neutral, dried over sodium sulphate and filtered, and the filtrate was concentrated. The crude product obtained in this manner was chromatographed in silica gel using a hexane/ethyl acetate gradient, and the appropriate fractions were combined and concentrated.

Workup

  1. waitafter 2 h at this temperature
  2. customthe cooling bath was removed
  3. addition375 mL of 2N aqueous hydrochloric acid and 1.25 L of ethyl acetate were added
  4. customThe organic phase was separated off
  5. washwashed with water until neutral,
  6. dry with materialdried over sodium sulphate
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-ec0c03a3948d4d5fb24b3a8a0ddb3704
Source dataset
uspto-grants-2016_04
Patent number
US09308282B2

Reaction notes

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